Although the toxic effects of cisplatinum on the kidney have been appreciated for some time, the renal handling of cisplatinum and the mechanism by which the renal toxicity occurs are still incompletely understood. These mechanisms could be more easily defined if the molecular sites of interaction of cisplatin were recognized. This project is designed to define how the kidney handles cisplatin under normal conditions and after various pretreatment or other experimental conditions. Inherent in this study is an attempt to localize the sites of interaction of cisplatin and its intracellular binding sites. This section reports the definitive animal study on renal handling of cisplatin, the effect of multiple treatments on renal handling of cisplatin, effect of changes in metabolic pH on cisplatin toxicity and distribution, studies that presumptively identify 2 low molecular weight binding sites for cisplatin, and interactions between cisplatin and drug metabolizing enzymes.